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Inhibition of HIV-1 infection of peripheral blood mononuclear cells by a monoclonal antibody that binds to phosphoinositides and induces secretion of β-chemokines

A murine IgG mAb, WR321, selected for the ability to bind to phosphatidylinositol-4-phosphate and phosphatidylinositol-4,5-bisphosphate, but an inability to bind to any of 17 other lipids, including phosphatidylinositol, was examined as a probe for studying interactions of HIV-1 with primary human p...

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Autores principales: Matyas, Gary R., Wieczorek, Lindsay, Bansal, Divya, Chenine, Agnes-Laurence, Sanders-Buell, Eric, Tovanabutra, Sodsai, Kim, Jerome H., Polonis, Victoria, Alving, Carl R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7173129/
https://www.ncbi.nlm.nih.gov/pubmed/21040700
http://dx.doi.org/10.1016/j.bbrc.2010.10.124
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author Matyas, Gary R.
Wieczorek, Lindsay
Bansal, Divya
Chenine, Agnes-Laurence
Sanders-Buell, Eric
Tovanabutra, Sodsai
Kim, Jerome H.
Polonis, Victoria
Alving, Carl R.
author_facet Matyas, Gary R.
Wieczorek, Lindsay
Bansal, Divya
Chenine, Agnes-Laurence
Sanders-Buell, Eric
Tovanabutra, Sodsai
Kim, Jerome H.
Polonis, Victoria
Alving, Carl R.
author_sort Matyas, Gary R.
collection PubMed
description A murine IgG mAb, WR321, selected for the ability to bind to phosphatidylinositol-4-phosphate and phosphatidylinositol-4,5-bisphosphate, but an inability to bind to any of 17 other lipids, including phosphatidylinositol, was examined as a probe for studying interactions of HIV-1 with primary human peripheral blood mononuclear cells. The WR321 mAb broadly neutralized CCR5-tropic strains of HIV-1 to prevent infection of the cells. The mAb also exhibited direct interaction with cells in the culture, resulting in secretion of chemokines that interfered with the interaction of HIV-1 virions with CCR5, the coreceptor for HIV-1 on the susceptible cells, leading to inhibition of infection by HIV-1. Phosphoinositides that are recognized by WR321 do not exist on the external surface of cells, but are concentrated on the inner surface (cytoplasmic leaflet) of the plasma membrane. Murine anti-phosphoinositide mAbs similar to WR321 have previously been directly microinjected into a variety of cultured cells, resulting in important changes in the functions of the cells. The present results suggest that binding of a mAb to phosphoinositides, resulting in secretion of β-chemokines into the culture medium and neutralization of infection by CCR5-tropic HIV-1 of nearby susceptible cells, occurred by uptake and binding of the mAb at an intracellular location in the cultured cells that then led to secretion of HIV-1-inhibitory β-chemokines.
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spelling pubmed-71731292020-04-22 Inhibition of HIV-1 infection of peripheral blood mononuclear cells by a monoclonal antibody that binds to phosphoinositides and induces secretion of β-chemokines Matyas, Gary R. Wieczorek, Lindsay Bansal, Divya Chenine, Agnes-Laurence Sanders-Buell, Eric Tovanabutra, Sodsai Kim, Jerome H. Polonis, Victoria Alving, Carl R. Biochem Biophys Res Commun Article A murine IgG mAb, WR321, selected for the ability to bind to phosphatidylinositol-4-phosphate and phosphatidylinositol-4,5-bisphosphate, but an inability to bind to any of 17 other lipids, including phosphatidylinositol, was examined as a probe for studying interactions of HIV-1 with primary human peripheral blood mononuclear cells. The WR321 mAb broadly neutralized CCR5-tropic strains of HIV-1 to prevent infection of the cells. The mAb also exhibited direct interaction with cells in the culture, resulting in secretion of chemokines that interfered with the interaction of HIV-1 virions with CCR5, the coreceptor for HIV-1 on the susceptible cells, leading to inhibition of infection by HIV-1. Phosphoinositides that are recognized by WR321 do not exist on the external surface of cells, but are concentrated on the inner surface (cytoplasmic leaflet) of the plasma membrane. Murine anti-phosphoinositide mAbs similar to WR321 have previously been directly microinjected into a variety of cultured cells, resulting in important changes in the functions of the cells. The present results suggest that binding of a mAb to phosphoinositides, resulting in secretion of β-chemokines into the culture medium and neutralization of infection by CCR5-tropic HIV-1 of nearby susceptible cells, occurred by uptake and binding of the mAb at an intracellular location in the cultured cells that then led to secretion of HIV-1-inhibitory β-chemokines. Elsevier 2010-11-26 2010-10-30 /pmc/articles/PMC7173129/ /pubmed/21040700 http://dx.doi.org/10.1016/j.bbrc.2010.10.124 Text en Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Matyas, Gary R.
Wieczorek, Lindsay
Bansal, Divya
Chenine, Agnes-Laurence
Sanders-Buell, Eric
Tovanabutra, Sodsai
Kim, Jerome H.
Polonis, Victoria
Alving, Carl R.
Inhibition of HIV-1 infection of peripheral blood mononuclear cells by a monoclonal antibody that binds to phosphoinositides and induces secretion of β-chemokines
title Inhibition of HIV-1 infection of peripheral blood mononuclear cells by a monoclonal antibody that binds to phosphoinositides and induces secretion of β-chemokines
title_full Inhibition of HIV-1 infection of peripheral blood mononuclear cells by a monoclonal antibody that binds to phosphoinositides and induces secretion of β-chemokines
title_fullStr Inhibition of HIV-1 infection of peripheral blood mononuclear cells by a monoclonal antibody that binds to phosphoinositides and induces secretion of β-chemokines
title_full_unstemmed Inhibition of HIV-1 infection of peripheral blood mononuclear cells by a monoclonal antibody that binds to phosphoinositides and induces secretion of β-chemokines
title_short Inhibition of HIV-1 infection of peripheral blood mononuclear cells by a monoclonal antibody that binds to phosphoinositides and induces secretion of β-chemokines
title_sort inhibition of hiv-1 infection of peripheral blood mononuclear cells by a monoclonal antibody that binds to phosphoinositides and induces secretion of β-chemokines
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7173129/
https://www.ncbi.nlm.nih.gov/pubmed/21040700
http://dx.doi.org/10.1016/j.bbrc.2010.10.124
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